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Creatine Supplementation (3 g/d) and Bone Health in Older Women: A 2-Year, Randomized, Placebo-Controlled Trial.
Sales, LP, Pinto, AJ, Rodrigues, SF, Alvarenga, JC, Gonçalves, N, Sampaio-Barros, MM, Benatti, FB, Gualano, B, Rodrigues Pereira, RM
The journals of gerontology. Series A, Biological sciences and medical sciences. 2020;(5):931-938
Abstract
BACKGROUND Creatine supplementation could be a nonexpensive, safe, and effective dietary intervention to counteract bone loss. The aim of this study was to investigate whether long-term creatine supplementation can improve bone health in older, postmenopausal women. METHODS A double-blind, placebo-controlled, parallel-group, randomized trial was conducted between November 2011 and December 2017 in Sao Paulo, Brazil. Two hundred postmenopausal women with osteopenia were randomly allocated to receive either creatine monohydrate (3 g/d) or placebo for 2 years. At baseline and after 12 and 24 months, we assessed areal bone mineral density (aBMD; primary outcome), lean and fat mass (through dual X-ray absorptiometry), volumetric BMD and bone microarchitecture parameters, biochemical bone markers, physical function and strength, and the number of falls and fractures. Possible adverse effects were self-reported. RESULTS Lumbar spine (p < .001), femoral neck (p < .001), and total femur aBMD (p = .032) decreased across time; however, no interaction effect was observed (all p > .050). Bone markers, microarchitecture parameters, and the number of falls/fractures were not changed with creatine (all p > .050). Lean mass and appendicular skeletal muscle mass increased throughout the intervention (p < .001), with no additive effect of creatine (p = .731 and p = .397, respectively). Creatine did not affect health-related laboratory parameters. CONCLUSION Creatine supplementation more than 2 years did not improve bone health in older, postmenopausal women with osteopenia, nor did it affect lean mass or muscle function in this population. This refutes the long-lasting notion that this dietary supplement alone has osteogenic or anabolic properties in the long run. CLINICAL TRIAL REGISTRY Clinicaltrials.gov: NCT: 01472393.
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Increased creatine demand during pregnancy in Arginine: Glycine Amidino-Transferase deficiency: a case report.
Alessandrì, MG, Strigini, F, Cioni, G, Battini, R
BMC pregnancy and childbirth. 2020;(1):506
Abstract
BACKGROUND Creatine (Cr), an amino acid derivative, is one of the most important sources of energy acting as both a spatial and temporal energy buffer through its phosphorylated analogue phosphocreatine (PCr) and creatine kinase (CK). Maternal Cr biosynthesis and metabolism seem to play an important role in pregnancy, as shown in preclinical and in healthy human pregnancy studies. Patients with Arginine:Glycine Amidino-Transferase deficiency (AGAT-d), due to the deficit of the first enzyme involved in Cr synthesis, are at a disadvantage due to their failure to synthesize Cr and their dependence on external intake, in contrast to normal subjects, where changes in Cr biosynthesis supply their needs. We report the outcomes of a pregnancy in an AGAT-d woman, and the challenge we faced in managing her treatment with oral Cr to ensure optimal conditions for her fetus. CASE PRESENTATION A 22-year-old AGAT-d woman referred to our Institute for the management of her first conception at 11 weeks of fetal gestational age. Sonographic monitoring at 20 w GA indicated a reduction of fetal growth, in particular of the head circumference that was below the 3rd centile. Biochemical monitoring of Cr in biological fluids of the mother revealed a decline of the Cr concentrations, in particular in the urine sample, requiring prompt correction of the Cr dose. At 35 weeks of gestation the patient delivered a male infant, heterozygous for GATM mutation, with normal brain Cr levels; at one year the baby achieved typical developmental milestones. CONCLUSIONS This rare pregnancy demonstrates that Cr levels in the blood and urine of the mother with AGAT-d decreased since the first months of gestation. The increase of the Cr daily dose administered to the mother seems to have produced beneficial effects also on the fetus.
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The addition of β-Hydroxy β-Methylbutyrate (HMB) to creatine monohydrate supplementation does not improve anthropometric and performance maintenance across a collegiate rugby season.
Mangine, GT, VanDusseldorp, TA, Hester, GM, Julian, JM, Feito, Y
Journal of the International Society of Sports Nutrition. 2020;(1):28
Abstract
BACKGROUND Muscular damage sustained while playing rugby may hinder performance across a season. β-Hydroxy β-Methylbutyrate (HMB) may help attenuate muscle damage and maintain lean mass and performance. This study sought to determine the effect of combining HMB with creatine monohydrate supplementation on measures of stress and muscle damage, body composition, strength and sprinting kinetics throughout a rugby season. METHODS This double-blind, cross-over investigation recruited 16 male collegiate rugby players to provide resting blood samples and complete assessments of body composition, strength and sprinting performance prior to their fall season (PREFALL). After testing, the athletes were matched for fat-free mass and assigned to consume one of two supplementation regimens for 6 weeks: 5 g HMB + 5 g creatine per day (HMB-Cr: 20.9 ± 1.1 years; 177 ± 2 cm; 88.4 ± 4.9 kg) or 5 g creatine + 5 g placebo per day (Cr: 21.4 ± 2.1 years; 179 ± 2 cm; 88.3 ± 4.9 kg). After 6 weeks (POSTFALL), PREFALL testing was repeated in 13 of the original 16 athletes before a 10-wk wash-out period. Athletes who returned for the spring season (n = 8) repeated all fall-season procedures and testing prior to (PRESPRING) and following (POSTSPRING) their 6-wk spring season, except they were assigned to the opposite supplementation regimen. RESULTS Linear mixed models with repeated measures revealed group x time interactions (p < 0.05) for observed for several measures but did not consistently and positively favor one group. During the fall season, knee extensor peak torque was reduced by 40.7 ± 28.1 Nm (p = 0.035) for HMB-Cr but remained consistent for Cr, and no group differences or changes were noted in the spring. In the spring, greater knee flexor rate of torque development (~ 149 Nm·sec- 1, p = 0.003) and impulse (~ 4.5 Nm·sec, p = 0.022) were observed in Cr at PRESPRING but not at POSTSPRING. Although significant interactions were found for cortisol concentrations, vastus lateralis pennation angle, and sprinting force, post-hoc analysis only revealed differences between fall and spring seasons. No other differences were observed. CONCLUSIONS The combination of HMB and creatine monohydrate supplementation does not provide a greater ergogenic benefit compared to creatine monohydrate supplementation alone. Body composition, strength, and sprinting ability did not change across the season with creatine monohydrate supplementation.
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Can Creatine Combat the Mental Fatigue-associated Decrease in Visuomotor Skills?
VAN Cutsem, J, Roelands, B, Pluym, B, Tassignon, B, Verschueren, JO, DE Pauw, K, Meeusen, R
Medicine and science in sports and exercise. 2020;(1):120-130
Abstract
PURPOSE The importance of the brain in sports was recently confirmed by the negative effect of mental fatigue (MF) on sport-specific psychomotor skills. Creatine supplementation improves strength but can also improve cognitive functioning. To explore the role of creatine in combating MF, we evaluated whether creatine supplementation counteracts the MF-associated impairment in sport-specific psychomotor skills. METHODS In 23°C, 14 healthy participants (4 females, 10 males; mean ± SD, age = 24 ± 3 yr, mass = 74 ± 13 kg, height = 179 ± 9 cm) performed a 90-min mentally fatiguing task (counterbalanced, crossover, and double-blinded; i.e., Stroop task) in two different conditions: after a 7-d creatine supplementation (CR; 20 g·d) and after a 7-d calcium lactate supplementation (placebo [PLAC]), separated by a 5-wk washout. In both conditions, a 7-min sport-specific visuomotor task, a dynamic handgrip strength endurance task, and a 3-min Flanker task was performed before and after the mentally fatiguing task. Physiological and perceptual responses were measured throughout the protocol. RESULTS Handgrip strength endurance was higher in CR compared with PLAC (P = 0.022). MF impaired visuomotor response time (+4.4%; P = 0.022) and Flanker accuracy (-5.0%; P = 0.009) in both conditions. Accuracy on the Stroop task was higher in CR compared with PLAC (+4.9%; P = 0.026). Within the perceptual and physiological parameters, only motivation and vigor (P ≤ 0.027) were lower in CR compared with PLAC. CONCLUSION Creatine supplementation improved physical (strength endurance) and prolonged cognitive (Stroop accuracy) performance, yet it did not combat MF-induced impairments in short sport-specific psychomotor or cognitive (Flanker) performance. These results warrant further investigation in the potential role of creatine in combating the MF-associated decrements in prolonged (e.g., 90-min soccer game) sport performance and suggest a role of brain phosphocreatine in MF.
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Effects of Creatine in Trained Athletes: A Meta-analysis of 21 Randomized Placebo-Controlled Trials.
Wu, Y, Hu, X, Chen, L
American journal of therapeutics. 2020;(5):e519-e523
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Lyn regulates creatine uptake in an imatinib-resistant CML cell line.
Okumu, DO, Aponte-Collazo, LJ, Dewar, BJ, Cox, NJ, East, MP, Tech, K, McDonald, IM, Tikunov, AP, Holmuhamedov, E, Macdonald, JM, et al
Biochimica et biophysica acta. General subjects. 2020;(4):129507
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Abstract
BACKGROUND Imatinib mesylate (imatinib) is the first-line treatment for newly diagnosed chronic myeloid leukemia (CML) due to its remarkable hematologic and cytogenetic responses. We previously demonstrated that the imatinib-resistant CML cells (Myl-R) contained elevated Lyn activity and intracellular creatine pools compared to imatinib-sensitive Myl cells. METHODS Stable isotope metabolic labeling, media creatine depletion, and Na+/K+-ATPase inhibitor experiments were performed to investigate the origin of creatine pools in Myl-R cells. Inhibition and shRNA knockdown were performed to investigate the specific role of Lyn in regulating the Na+/K+-ATPase and creatine uptake. RESULTS Inhibition of the Na+/K+-ATPase pump (ouabain, digitoxin), depletion of extracellular creatine or inhibition of Lyn kinase (ponatinib, dasatinib), demonstrated that enhanced creatine accumulation in Myl-R cells was dependent on uptake from the growth media. Creatine uptake was independent of the Na+/creatine symporter (SLC6A8) expression or de novo synthesis. Western blot analyses showed that phosphorylation of the Na+/K+-ATPase on Tyr 10 (Y10), a known regulatory phosphorylation site, correlated with Lyn activity. Overexpression of Lyn in HEK293 cells increased Y10 phosphorylation (pY10) of the Na+/K+-ATPase, whereas Lyn inhibition or shRNA knockdown reduced Na+/K+-ATPase pY10 and decreased creatine accumulation in Myl-R cells. Consistent with enhanced uptake in Myl-R cells, cyclocreatine (Ccr), a cytotoxic creatine analog, caused significant loss of viability in Myl-R compared to Myl cells. CONCLUSIONS These data suggest that Lyn can affect creatine uptake through Lyn-dependent phosphorylation and regulation of the Na+/K+-ATPase pump activity. GENERAL SIGNIFICANCE These studies identify kinase regulation of the Na+/K+-ATPase as pivotal in regulating creatine uptake and energy metabolism in cells.
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Repeated Application of a Novel Creatine Cream Improves Muscular Peak and Average Power in Male Subjects.
Whinton, AK, Donahoe, K, Gao, R, Thompson, KMA, Aubry, R, Saunders, TJ, Johnston, A, Chilibeck, PD, Burr, JF
Journal of strength and conditioning research. 2020;(9):2482-2491
Abstract
Whinton, AK, Donahoe, K, Gao, R, Thompson, KMA, Aubry, R, Saunders, TJ, Johnston, A, Chilibeck, PD, and Burr, JF. Repeated application of a novel creatine cream improves muscular peak and average power in male subjects. J Strength Cond Res 34(9): 2482-2491, 2020-Using a multicenter, randomized controlled trial, (N = 123, age 23 ± 4 years) we sought to determine whether administration of a novel, topical creatine supplement could improve muscular performance after acute and repeated (7-day) exposure. To study the acute performance enhancing effects of the supplement, subjects completed 5 sets of 15 maximal concentric single-leg knee extensions with and without the application of a low- (low dose [LD]-3.5 ml) or high-dose (high dose [HD]-7 ml) topical creatine cream. After a wash-out period, subjects had one leg randomized to receive either the creatine or placebo cream, with further randomization into an oral creatine or placebo supplement group. Subjects completed 5 sets of 15 maximal concentric single leg knee extensions before and after the supplementation protocol. After acute application, no significant differences in peak power (LD: 252 ± 93 W, HD: 261 ± 100 W, p = 0.21), average power (LD: 172 ± 65 W, HD: 177 ± 69 W, p = 0.78), or fatigue index (LD: 13.4 ± 10.6%, HD: 14 ± 11.9%, p = 0.79) were observed between experimental and placebo creams (peak power: LD: 244 ± 76 W, HD: 267 ± 109 W; average power: LD: 168 ± 57 W, HD: 177 ± 67 W; fatigue index: LD: 12.4 ± 9.6%, HD: 12.8 ± 10.6%) or when controlling for sex. After the 7-day supplementation protocol, a significant increase in average power (creatine: 203 ± 61-220 ± 65 W, placebo: 224 ± 61-214 ± 61 W) and peak power (creatine: 264 ± 73-281 ± 80 W, placebo: 286 ± 79-271 ± 73 W) in the leg receiving creatine cream was observed in male subjects. No differences were observed in female subjects. The topical creatine cream did not enhance measures of muscle performance after acute application, but was able to improve peak and average power in male subjects after 7 consecutive days of application.
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Creatine is a Conditionally Essential Nutrient in Chronic Kidney Disease: A Hypothesis and Narrative Literature Review.
Post, A, Tsikas, D, Bakker, SJL
Nutrients. 2019;(5)
Abstract
To accommodate the loss of the plethora of functions of the kidneys, patients with chronic kidney disease require many dietary adjustments, including restrictions on the intake of protein, phosphorus, sodium and potassium. Plant-based foods are increasingly recommended as these foods contain smaller amounts of saturated fatty acids, protein and absorbable phosphorus than meat, generate less acid and are rich in fibers, polyunsaturated fatty acids, magnesium and potassium. Unfortunately, these dietary recommendations cannot prevent the occurrence of many symptoms, which typically include fatigue, impaired cognition, myalgia, muscle weakness, and muscle wasting. One threat coming with the recommendation of low-protein diets in patients with non-dialysis-dependent chronic kidney disease (CKD) and with high-protein diets in patients with dialysis-dependent CKD, particularly with current recommendations towards proteins coming from plant-based sources, is that of creatine deficiency. Creatine is an essential contributor in cellular energy homeostasis, yet on a daily basis 1.6-1.7% of the total creatine pool is degraded. As the average omnivorous diet cannot fully compensate for these losses, the endogenous synthesis of creatine is required for continuous replenishment. Endogenous creatine synthesis involves two enzymatic steps, of which the first step is a metabolic function of the kidney facilitated by the enzyme arginine:glycine amidinotransferase (AGAT). Recent findings strongly suggest that the capacity of renal AGAT, and thus endogenous creatine production, progressively decreases with the increasing degree of CKD, to become absent or virtually absent in dialysis patients. We hypothesize that with increasing degree of CKD, creatine coming from meat and dairy in food increasingly becomes an essential nutrient. This phenomenon will likely be present in patients with CKD stages 3, 4 and 5, but will likely be most pronouncedly present in patients with dialysis-dependent CKD, because of the combination of lowest endogenous production of creatine and unopposed losses of creatine into the dialysate. It is likely that these increased demands for dietary creatine are not sufficiently met. The result of which, may be a creatine deficiency with important contributions to the sarcopenia, fatigue, impaired quality of life, impaired cognition, and premature mortality seen in CKD.
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Creatine supplementation improves performance above critical power but does not influence the magnitude of neuromuscular fatigue at task failure.
Schäfer, LU, Hayes, M, Dekerle, J
Experimental physiology. 2019;(12):1881-1891
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Abstract
NEW FINDINGS What is the central question of this study? Does the magnitude of neuromuscular fatigue depend on the amount of work done (W') at task failure when cycling above critical power (CP)? What is the main finding and its importance? Creatine supplementation increases W' and enhances supra-CP performance, but induces similar magnitudes of neuromuscular fatigue at task failure compared to placebo. Increased W' does not lead to higher levels of neuromuscular fatigue. This supports the notion of a critical level of neuromuscular fatigue at task failure and challenges a direct causative link between W' depletion and neuromuscular fatigue. ABSTRACT The present study examined the effect of creatine supplementation on neuromuscular fatigue and exercise tolerance when cycling above critical power (CP). Eleven males performed an incremental cycling test with four to five constant-load trials to task failure (TTF) to obtain asymptote (CP) and curvature constant (W') of the power-duration relationship, followed by three constant-load supra-CP trials: (1) one TTF following placebo supplementation (PLA); (2) one TTF following creatine supplementation (CRE); and (3) one trial of equal duration to PLA following creatine supplementation (ISO). Neuromuscular assessment of the right knee extensors was performed pre- and post-exercise to measure maximal voluntary contraction (MVC), twitch forces evoked by single (Qpot ) and paired high- (PS100) and low- (PS10) frequency stimulations and voluntary activation. Creatine supplementation increased TTF in CRE vs. PLA by ∼11% (P = 0.017) and work done above CP by ∼10% (P = 0.015), with no difference (P > 0.05) in reductions in MVC (-24 ± 8% vs. -20 ± 9%), Qpot (-39 ± 13% vs. -32 ± 14%), PS10 (-42 ± 14% vs. -36 ± 13%), PS100 (-25 ± 10% vs. -18 ± 12%) and voluntary activation (-7 ± 8% vs. -5 ± 7%). No significant difference was found between ISO and either PLA or CRE (P > 0.05). These findings suggest similar levels of neuromuscular fatigue can be found following supra-CP cycling despite increases in performance time and amount of work done above CP, supporting the notion of a critical level of neuromuscular fatigue and challenging a direct causative link between W' depletion and neuromuscular fatigue.
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Creatine monohydrate supplementation during eight weeks of progressive resistance training increases strength in as little as two weeks without reducing markers of muscle damage.
Kaviani, M, Abassi, A, Chilibeck, PD
The Journal of sports medicine and physical fitness. 2019;(4):608-612
Abstract
BACKGROUND Creatine supplementation (Cr) increases strength during resistance training, but the time course of this strength increase is unclear. The aim was to determine the precise time course by which Cr could increase strength and whether Cr prevents muscle damage during eight weeks of resistance training. METHODS Young males were randomized (double blind) to Cr (N.=9, 0.07g/kg/d) and placebo (N.=9) during 8-weeks of resistance training (3 d/week). Strength was assessed across six exercises every two weeks. Venous blood samples obtained at baseline, and 24 and 48 hours after the final resistance training session were assessed for creatine kinase [CK] and lactate dehydrogenase [LDH] as measures of muscle damage. RESULTS Strength was significantly higher in the Cr versus placebo group (P<0.05) after two weeks of training for three of the six exercises (bench press, leg press, shoulder press). By the end of the eight weeks of training, strength was significantly higher in the Cr versus placebo group (P<0.05) for four of the six exercises (bench press, leg press, shoulder press, and triceps extension, but not biceps curl or lat-pulldown). Creatine supplementation did not prevent muscle damage. Indeed, muscle damage markers increased in the Cr compared to placebo group (P<0.05). CONCLUSIONS Cr increased muscular strength in as little as two weeks during a resistance training program; however, this was not accompanied by decreased muscle damage. Greater muscle damage with Cr may be due to a greater training intensity enabled by Cr supplementation. This might lead to greater protein turnover and enhanced muscle adaptation.